Local Organ Procurement Organization Research Articles

Characterization of Transplant Center Decisions to Allocate Kidneys to Candidates With Lower Waiting List Priority

Allocation of deceased donor kidneys is meant to follow a ranked match-run list of eligible candidates, but transplant centers with a 1-to-1 relationship with their local organ procurement organization have full discretion to decline offers for higher-priority candidates and accept them for lower-ranked candidates at their center. To describe the practice and frequency of transplant centers placing deceased donor kidneys with candidates who are not the highest rank at their center according to the allocation algorithm. This retrospective cohort study used 2015 to 2019 organ offer data from US transplant centers with a 1-to-1 relationship with their local organ procurement organization, following candidates for transplant events from January 2015 to December 2019. Participants were deceased kidney donors with a single match-run and at least 1 kidney transplanted locally and adult, first-time, kidney-only transplant candidates receiving at least 1 offer for a locally transplanted deceased donor kidney. Data were analyzed from March 1, 2022 to March 28, 2023. Demographic and clinical characteristics of donors and recipients. The outcome of interest was kidney transplantation into the highest-priority candidate (defined as transplanted after zero declines for local candidates in the match-run) vs a lower-ranked candidate. This study assessed 26 579 organ offers from 3136 donors (median [IQR] age, 38 [25-51] years; 2903 [62%] men) to 4668 recipients. Transplant centers skipped their highest-ranked candidate to place kidneys further down the match-run for 3169 kidneys (68%). These kidneys went to a median (IQR) of the fourth- (third- to eighth-) ranked candidate. Higher kidney donor profile index (KDPI; higher score indicates lower quality) kidneys were less likely to go to the highest-ranked candidate, with 24% of kidneys with KDPI of at least 85% going to the top-ranked candidate vs 44% of KDPI 0% to 20% kidneys. When comparing estimated posttransplant survival (EPTS) scores between the skipped candidates and the ultimate recipients, kidneys were placed with recipients with both better and worse EPTS than the skipped candidates, across all KDPI risk groups. In this cohort study of local kidney allocation at isolated transplant centers, we found that centers frequently skipped their highest-priority candidates to place kidneys further down the allocation prioritization list, often citing organ quality concerns but placing kidneys with recipients with both better and worse EPTS with nearly equal frequency. This occurred with limited transparency and highlights the opportunity to improve the matching and offer algorithm to improve allocation efficiency.

V08-01 ROBOTIC BLADDER AUTOTRANSPLANTATION IN A BRAIN-DEAD HEART-BEATING DECEASED DONOR: WET RUN BEFORE A FIRST-IN-HUMAN CLINICAL TRIAL

You have accessJournal of UrologyCME1 Apr 2023V08-01 ROBOTIC BLADDER AUTOTRANSPLANTATION IN A BRAIN-DEAD HEART-BEATING DECEASED DONOR: WET RUN BEFORE A FIRST-IN-HUMAN CLINICAL TRIAL Nima Nassiri, Giovanni Cacciamani, David Ginsberg, Evgeniy Kreydin, Andre Abreu, Mihir Desai, Monish Aron, Yasir Qazi, Yuri Genyk, and Inderbir Gill Nima NassiriNima Nassiri More articles by this author , Giovanni CacciamaniGiovanni Cacciamani More articles by this author , David GinsbergDavid Ginsberg More articles by this author , Evgeniy KreydinEvgeniy Kreydin More articles by this author , Andre AbreuAndre Abreu More articles by this author , Mihir DesaiMihir Desai More articles by this author , Monish AronMonish Aron More articles by this author , Yasir QaziYasir Qazi More articles by this author , Yuri GenykYuri Genyk More articles by this author , and Inderbir GillInderbir Gill More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000003306.01AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: Bladder transplantation has not yet been successfully performed. Technical challenges include complicated deep pelvic vascular anatomy, limited visualization, and procedural complexity. In preparation for a first-in-human clinical trial of bladder transplantation (NCT05462561), we performed a robotic vascularized composite bladder allograft (VCBA) autotransplantation in a brain-dead heart-beating research donor. METHODS: An appropriate research donor was identified by our local organ procurement organization. VCBA autotransplantation was performed, including VCBA dissection, extracorporeal back-tabling, vascular reanastomoses, and vesicourethral anastomosis. A robotic approach was necessary to optimize visualization in the deep pelvis and maximally preserve allograft perfusion. The primary objective was to develop the stepwise procedure and gauge its technical success, defined by autograft perfusion by direct visual inspection and indigo-cyanine green (ICG) fluorescence. Secondary objectives included intraoperative parameters (operative times, warm ischemia time, and EBL). IRB (HS-21-00162) approval was obtained. RESULTS: Technical success, defined by adequate autograft perfusion after vascular anastomosis, was achieved. In the brain-dead heart beating donor, the technical maneuvers were well tolerated, with intra-operative hemodynamic stability (Table 1). Operative time was 670 min. Visual inspection revealed a pink, healthy bladder and patent vascular anastomoses, with diffuse ICG uptake. CONCLUSIONS: This is the first documented case of robotic bladder autotransplantation, performed in a brain-dead heart-beating research donor as a necessary preclinical step towards a first-in-human trial of bladder transplantation (NCT05462561). Technical feasibility was demonstrated, and vascular viability was confirmed by ICG uptake. The robotic approach was necessary for fine vascular dissection in the deep pelvis. Source of Funding: This study has been supported by a clinical research grant from the OneLegacy Foundation. © 2023 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 209Issue Supplement 4April 2023Page: e748 Advertisement Copyright & Permissions© 2023 by American Urological Association Education and Research, Inc.MetricsAuthor Information Nima Nassiri More articles by this author Giovanni Cacciamani More articles by this author David Ginsberg More articles by this author Evgeniy Kreydin More articles by this author Andre Abreu More articles by this author Mihir Desai More articles by this author Monish Aron More articles by this author Yasir Qazi More articles by this author Yuri Genyk More articles by this author Inderbir Gill More articles by this author Expand All Advertisement PDF downloadLoading ...

295 Identification of Proteomic Biomarkers in Puerto Ricans with Pancreatic Cancer

OBJECTIVES/GOALS: Our objective is to establish a proteomic protein labeling method from tumor tissue and blood samples obtained from patients undergoing surgery for pancreatic cancer in Puerto Rico. Our goal is to discover potential biomarkers in the patient tumor/blood samples that are not expressed in normal control samples obtained from potential organ donors. METHODS/STUDY POPULATION: A pilot study with ten patients undergoing surgery for pancreatic cancer will obtain tumor tissue and blood samples. Protein extracts isolated from tissue/cells will be reduced, alkylated, and digested overnight. Samples will be labeled with TMT reagents and mixed before fractionation and cleanup. Labeled samples will be analyzed with a high-resolution Orbitrap LC-MS/MS before data analysis to identify peptides and quantify the reporter ions. The altered proteins will be analyzed by ELISA to confirm their presence. The protein arrangements will be compared with results from proteomic profile banks to assess their prevalence. As controls, parallel protein analyses will be performed on normal tissue/blood samples from organ donors, facilitated by our local organ procurement organization. RESULTS/ANTICIPATED RESULTS: We anticipate finding proteogenomic material defining PC and new proteomic subtypes not previously described in this population. In addition, studying protein overexpression and underexpression can identify relevant genes and potential biomarkers. We hypothesize that PC in the Hispanic population will show slight variations in tumor protein expression than in other populations, which could lead to the discovery of a new Hispanic-specific biomarker. DISCUSSION/SIGNIFICANCE: We expect to provide essential information that will influence the next steps in developing future screening tests. Identifying specific proteins with the potential to become a preventive test should eventually lead to a reduction in morbidity and mortality of PC. The results of this work should lay the foundation that can guide future research.

Characteristics of donor lungs declined on site and impact of lung allocation policy change

ObjectiveNational and institutional data suggest an increase in organ discard rate (donor lungs procured but not implanted) after a new lung allocation policy was introduced in 2017. However, this measure does not include on-site decline rate (donor lungs declined intraoperatively). The objective of this study is to examine the impact of the allocation policy change on on-site decline. MethodsWe used a Washington University (WU) and our local organ procurement organization (Mid-America Transplant [MTS]) database to abstract data on all accepted lung offers from 2014 to 2021. An on-site decline was defined as an event in which the procuring team declined the organs intraoperatively, and the lungs were not procured. Logistic regression models were used to investigate potentially modifiable reasons for decline. ResultsThe overall study cohort comprised 876 accepted lung offers, of which 471 donors were at MTS with WU or others as the accepting center and 405 at other organ procurement organizations with WU as the accepting center. At MTS, the on-site decline rate increased from 4.6% to 10.8% (P = .01) after the policy change. Given the greater likelihood of non-local organ placement and longer travel distance after policy change, the estimated cost of each on-site decline increased from $5727 to $9700. In the overall group, latest partial pressure of oxygen (odds ratio [OR], 0.993; 95% confidence interval [CI], 0.989-0.997), chest trauma (OR, 2.474; CI, 1.018-6.010), chest radiograph abnormality (OR, 2.902; CI, 1.289-6.532), and bronchoscopy abnormality (OR, 3.654; CI, 1.813-7.365) were associated with on-site decline, although lung allocation policy era was unassociated (P = .22). ConclusionsWe found that nearly 8% of accepted lungs are declined on site. Several donor factors were associated with on-site decline, although lung allocation policy change did not have a consistent impact on on-site decline.

Potential Role of Computed Tomography Volumetry in Size Matching in Lung Transplantation

Accumulated knowledge on the outcomes related to size mismatch in lung transplantation derives from predicted total lung capacity equations rather than individualized measurements of donors and recipients. The increasing availability of computed tomography (CT) makes it possible to measure the lung volumes of donors and recipients before transplantation. We hypothesize that CT-derived lung volumes predict a need for surgical graft reduction and primary graft dysfunction. Donors from the local organ procurement organization and recipients from our hospital from 2012 to 2018 were included if their CT exams were available. The CT lung volumes and plethysmography total lung capacity were measured and compared with predicted total lung capacity using Bland Altman methods. We used logistic regression to predict the need for surgical graft reduction and ordinal logistic regression to stratify the risk for primary graft dysfunction. A total of 315 transplant candidates with 575 CT scans and 379 donors with 379 CT scans were included. The CT lung volumes closely approximated plethysmography lung volumes and differed from the predicted total lung capacity in transplant candidates. In donors, CT lung volumes systematically underestimated predicted total lung capacity. Ninety-four donors and recipients were matched and transplanted locally. Larger donor and smaller recipient lung volumes estimated by CT predicted a need for surgical graft reduction and were associated with higher primary graft dysfunction grade. The CT lung volumes predicted the need for surgical graft reduction and primary graft dysfunction grade. Adding CT-derived lung volumes to the donor-recipient matching process may improve recipients' outcomes.

Organ donation after self-inflicted injury: A single institution analysis.

This study sought to determine the contribution of self-inflicted injury-related deaths to local organ donation rates and analyze contributing factors. A retrospective review of adult patients with traumatic self-inflicted injuries was performed at a Level I trauma center from 2013 to 2017. Data were obtained from the institutional trauma registry and cross-referenced with the local organ procurement organization (OPO). Referral rates were analyzed and outcomes, demographics and injury characteristics were compared between patients who underwent donation versus those who did not. 142 adult patients presented with traumatic self-inflicted injury, and 100 (70.4%) had referral calls made to the local OPO. These patients were predominantly male (83%), and gunshot injuries accounted for 75% of all mechanisms. Sixty-four percent had organ referrals versus tissue referrals (34%), and 17 (26.6%) of those patients went on to donate. The median number of organs procured was 4 [IQR 0-5]. In multivariate analysis, for each year increase in age, patients were less likely to have an organ referral (OR=.96 [95% CI .93-.99]; p=.0134) and less likely to undergo donation (OR=.95 [95% CI .90-.99]; p=.0308). Self-inflicted injury, though tragic, may provide a significant contribution to the limited organ donor registry.

Organ procurement organization and university-based respiratory care program partnership to develop student internships.

IntroductionHealth care providers working as organ recovery coordinators (ORC) in the United States have diverse backgrounds and many of the skills needed for the position are obtained during on-the-job training. Some students in health care programs express interest in the organ procurement field but have limited experience and knowledge regarding organ procurement practices. In response to this, a partnership was developed between an undergraduate respiratory care (RC) program and its local organ procurement organization (OPO) to develop and initiate an internship designed to educate students regarding organ procurement.ApproachThe 160-h internship was developed with collaboration between the OPO administration and faculty from the university RC program, which closely followed the OPO’s formalized per diem ORC orientation model. Student reflective journals were qualitatively analyzed to determine the shared experiences during the OPO internships.FindingsOne RC student participated in the internship in 2017 and three RC students participated in 2019. The student interns actively participated in organ donor management in the critical care and surgical settings with the scheduled ORCs. Student progression of emotional competence and leadership were demonstrated throughout the internship.DiscussionThe OPO internship benefited RC students by providing opportunities for professional development that may not be available during their typical clinical rotations and strengthened their critical care skills and emotional competence.ConclusionEmployment as an ORC is an emerging role for respiratory therapists. Offering educational opportunities such as internships in emerging roles promotes student development and autonomy while promoting the respiratory therapy profession.

Moving From Organ Donation to Knowledge Donation: A Novel Opportunity for Surgical Education Following Organ Donation.

The objective of this article is to share how our institution implemented the use of organ donors for surgical education following organ recovery. Despite technological advances, realistic surgical simulation models are lacking, leaving little opportunity to practice a procedure prior to performance on a living patient. Utilization of organ donors following organ donation offers an opportunity for life-like surgical simulation. We developed a pathway to use organ donor tissue in the post-recovery period for robotic simulation. We obtained support from our local Institutional Review Board, Ethics Committee, and organ procurement organization to create a “knowledge donor” program. Our knowledge donation program provided learners hands-on experience with a novel procedure and also provided organ donors another opportunity to express their altruism. We found that the process was well accepted by donor families and learners. We implemented a knowledge donation program at our hospital that provides valuable surgical experience. We discuss future directions for knowledge donation at our institution.

Local versus distant lung donor procurement does not influence short-term clinical outcomes

ObjectiveThe purpose of this study was to recognize clinically meaningful differences in lung transplant outcomes based on local or distant lung procurement. This could identify if the lung allocation policy change would influence patient outcomes. MethodsThis single-center retrospective cohort study analyzed adult patients who underwent lung transplant from 2006 to 2017. Donor and recipient data were abstracted from a collaborative, prospective registry shared by our local organ procurement organization, and tertiary medical center. Short-term outcomes, 1-year survival, and hospitalization costs were compared between local and distant lung transplants defined by donor service area. ResultsOf the 722 lung transplants performed, 392 (54%) had local donors and 330 (46%) had distant donors. Donors were similar in age and cause of death. Recipients were significantly different in diagnosis and local recipients had lower median lung allocation scores (local, 37.3 and distant, 44.9; P < .01). Distant lung transplants had longer total ischemic times (local, 231 ± 52 minutes and distant, 313 ± 48 minutes; P < .01). The rate of major complications, length of hospital stay, and 1-year survival were similar between groups. Distant lung transplants were associated with higher median overall cost (local, $183,542 and distant, $229,871; P < .01). Local lung transplants were more likely to be performed during daytime (local, 333 out of 392 [85%] and distant, 291 out of 330 [61%]; P < .01). ConclusionsLocal lung transplants are associated with shorter ischemic times, lower cost, and greater likelihood of daytime surgery. Short- and intermediate-term outcomes are similar for lung transplants from local and distant donors. The new lung allocation policy, with higher proportion of distant lung transplants, is likely to incur greater costs but provide similar outcomes.

Factors that affect consent rate for organ donation after brain death: A 12-year registry

ObjectiveTo account for factors affecting family approach and consent for organ donation after brain death (BD). Material and methodsA prospective cohort study in a large, tertiary, urban hospital, where we reviewed the database of all brain-dead patients between January 2006 and December 2017 cross-matched with local organ procurement organization (OPO) records. ResultsTwo-hundred sixty-six brain-dead patients were included (55% African Americans (AAs)). Two-hundred twenty-two were approached for donation. The reason for not approaching families was medical exclusion due to cancer or multi-organ failure. Patient demographics or religion were not associated with approaching families. Lower creatinine level was the only independent factor associated with higher approach. Consent rate for organ donation was 72.5%. Consent was significantly higher in Caucasians (89% vs 62% for AAs), younger patients (46.7 vs 52.5 years old), in patients with lower creatinine at time of death (1.7 vs 2.4 mg/dL), patients for whom apnea testing was completed (92% vs 80%) and patients with diabetes insipidus (DI) (72% vs 54%). There was no significant relationship between consent and patient gender, admission diagnosis, number of examinations or completion of a confirmatory test. In a logistic regression model, only AA race independently predicted consent for donation (odds, 95% CI, 0.27, 0.12–0.57 p < .001). In a different model, apnea test completion was an additional independent predictor (3.66, 1.28–10.5 p = .015). ConclusionsApproaching families for organ donation consent was associated with medical suitability only and not with demographic or religious characteristics. AAs were 3.7 times less likely to consent for organ donation than non-AAs. Completion of apnea testing was associated with higher consent rates, an observation that needs to be explored in future studies documenting the effect on bedside family presence during this test.

Ultra-short duration direct acting antiviral prophylaxis to prevent virus transmission from hepatitis C viremic donors to hepatitis C negative kidney transplant recipients.

We conducted an adaptive design single-center pilot trial between October 2017 and November 2018 to determine the safety and efficacy of ultra-short-term perioperative pangenotypic direct acting antiviral (DAA) prophylaxis for deceased hepatitis C virus (HCV)-nucleic acid test (NAT) positive donors to HCV negative kidney recipients (D+/R-). In Group 1, 10 patients received one dose of SOF/VEL (sofusbuvir/velpatasvir) pretransplant and one dose on posttransplant Day 1. In Group 2A (N=15) and the posttrial validation (Group 2B; N=25) phase, patients received two additional SOF/VEL doses (total 4) on Days 2 and 3 posttransplant. Development of posttransplant HCV transmission triggered 12-week DAA therapy. For available donor samples (N=27), median donor viral load was 1.37E+06IU/mL (genotype [GT]1a: 70%; GT2: 7%; GT3: 23%). Overall viral transmission rate was 12% (6/50; Group 1:30% [3/10]; Group 2A:13% [2/15]; Group 2B:4% [1/25]). For the 6 viremic patients, 5 (83%) achieved sustained virologic response (3 with first-line DAA therapy; and two after retreatment with second-line DAA). At a median follow-up of 8months posttransplant, overall patient and allograft survivals were 98%, respectively. The 4-day strategy reduced viral transmission to 7.5% (3/40; 95% confidence interval [CI]: 1.8%-20.5%) and could result in avoidance of prolonged posttransplant DAA therapy for most D+/R-transplants.

Single Port Robotic Extra-peritoneal Dual Kidney Transplantation: Initial Preclinical Experience and Description of the Technique

ObjectiveTo describe the surgical technique for single-port robotic extraperitoneal dual kidney transplantation (DKT) using the SP surgical system (Intuitive Surgical, Sunnyvale, CA, USA) in a preclinical model. MethodsIn 1 male cadaver, the SP Surgical System was used to perform an extraperitoneal DKT. Kidney grafts were obtained from the local organ procurement organization, after being declined by all transplant centers. Kidneys were benched and wrapped in cold sponges. A periumbilical midline incision was performed. A kidney-shaped balloon was inserted through the incision to create the extraperitoneal space. SP robot was docked followed by dissection of iliac vessels bilaterally. The robot was undocked and the first graft was inserted through the wound retractor. The robot was re-docked and the renal vein anastomosis to external iliac vein was performed followed by renal artery anastomosis to external iliac artery using 5-0 monofilament sutures. Ureteroneocystostomy was performed using the Lich-Gregoir technique over a trasplant stent. Same steps were replicated for the left kidney transplant. Once procedures were done, kidneys were then harvested with the iliac vessels to examine the quality of the anastomosis. ResultsThe surgical procedure was completed successfully without the need of additional port or conversion to standard approach. Total bench kidney time was 30 minutes with overall transplantation time of 130 and 115 minutes of the right and left kidney, respectively. ConclusionWe demonstrated the feasibility of single-port extraperitoneal DKT using the novel SP robotic platform. Limitations include the preclinical model. Further assessment is necessary in a truly clinical setting.

Technique for Rapid Hand Transplant Donor Procurement Through the Elbow.

Background: Hand and distal forearm allotransplantation has advanced over the last 20 years from experimental to a viable treatment option for bilateral upper extremity amputation. Despite widespread growth of this field, there are few technical reports that elaborate the details of donor arm procurement. This article details a technique for rapid donor procurement through the elbow for mid to distal forearm-level hand allograft procurement. Methods: Nine arm procurements were performed on deceased tissue-only donors provided by the local organ procurement organization, including two bilateral and five unilateral cases. Technique highlights include using a fishmouth incision through the lateral and medical epicondyles, identification of the neurovascular structures, and disarticulating the elbow joint. Results: Procuring through the elbow provides straightforward anatomy, bypasses the need to cut through bone, and allows tissue allotransplantation teams to achieve procurement, flushing, and packaging within 20 minutes. Conclusions: Procurement through the elbow is a simple procedure that streamlines the process for multi-organ donors by minimizing the time needed for hand allograft procurement. Team coordination and surgical rehearsals are essential for successful hand and upper extremity procurement and allotransplantation.

Human Hearts Declined for Transplant Were Resuscitated on the Visible Heart® Apparatus

Purpose Improved utilization of donor hearts would benefit chronic heart failure patients awaiting transplant. Limitations to cardiac allograft preservation include ischemic time, donor organ quality, and accurate graft assessment. We hypothesized that human hearts declined for transplant may be resuscitated after varied ischemic times. The unique studies performed within the Visible Heart® Laboratory for over two decades have provided unique insights relative to optimizing large mammalian functions post-cardioplegia. Methods Human hearts declined for transplant were utilized for research at the Visible Heart® Laboratory in coordination with the local organ procurement organization. Donor hearts were procured in standard fashion using 2L cardioplegia solution, and storage on ice. Hearts were delivered within 4-10 hours and cannulated for perfusion in Langendorf, right-sided, or 4-chamber working modes. Next, hearts were perfused with a warmed, oxygenated Kreb-Henseleit perfusate. These hearts were deemed non-viable for transplant for a variety of factors. Hemodynamic parameters, functional endoscopic videos, and electrocardiographic parameters have been recorded. All hearts were perfusion-fixed in formaldehyde and preserved in the Visible Heart® Library. Results Eighty-three human hearts declined for transplant were reanimated on the Visible Heart® Apparatus: varied hemodynamic functions were recorded. Average donor age was 57 years (7 to 91 yrs). Fifty percent (50%) of donors were female. Average cold ischemic time was 402 minutes (126-678 minutes). All hearts achieved pulsatile perfusion, and evidence of EKG rhythm. Conclusion This work demonstrates the unique capabilities of the Visible Heart® Laboratory: the abilities to reanimate human hearts and investigate relative electrophysioligical and hemodynamic behaviors has utility for determining if some human hearts declined for transplant were in fact viable, or could benefit from post-conditoning. Hence, this work provides encouragement for expanding the utilization of donor hearts available for transplant. Future work will focus on improved preservation techniques (i.e., various cardioplegia agents, warm perfusion vs cold storage), novel pharmacologic pre- and post-conditioning agents, and improved assessment of donor hearts during preservation. Improved utilization of donor hearts would benefit chronic heart failure patients awaiting transplant. Limitations to cardiac allograft preservation include ischemic time, donor organ quality, and accurate graft assessment. We hypothesized that human hearts declined for transplant may be resuscitated after varied ischemic times. The unique studies performed within the Visible Heart® Laboratory for over two decades have provided unique insights relative to optimizing large mammalian functions post-cardioplegia. Human hearts declined for transplant were utilized for research at the Visible Heart® Laboratory in coordination with the local organ procurement organization. Donor hearts were procured in standard fashion using 2L cardioplegia solution, and storage on ice. Hearts were delivered within 4-10 hours and cannulated for perfusion in Langendorf, right-sided, or 4-chamber working modes. Next, hearts were perfused with a warmed, oxygenated Kreb-Henseleit perfusate. These hearts were deemed non-viable for transplant for a variety of factors. Hemodynamic parameters, functional endoscopic videos, and electrocardiographic parameters have been recorded. All hearts were perfusion-fixed in formaldehyde and preserved in the Visible Heart® Library. Eighty-three human hearts declined for transplant were reanimated on the Visible Heart® Apparatus: varied hemodynamic functions were recorded. Average donor age was 57 years (7 to 91 yrs). Fifty percent (50%) of donors were female. Average cold ischemic time was 402 minutes (126-678 minutes). All hearts achieved pulsatile perfusion, and evidence of EKG rhythm. This work demonstrates the unique capabilities of the Visible Heart® Laboratory: the abilities to reanimate human hearts and investigate relative electrophysioligical and hemodynamic behaviors has utility for determining if some human hearts declined for transplant were in fact viable, or could benefit from post-conditoning. Hence, this work provides encouragement for expanding the utilization of donor hearts available for transplant. Future work will focus on improved preservation techniques (i.e., various cardioplegia agents, warm perfusion vs cold storage), novel pharmacologic pre- and post-conditioning agents, and improved assessment of donor hearts during preservation.

Abstract B153: Human NK cell distribution memory and residence in tissue sites

Abstract Natural killer (NK) cells are innate immune cells with the ability to kill tumor cells without prior exposure. NK cells express multiple activating and inhibitory receptors in addition to the low-affinity immunoglobulin G binding receptor CD16. Accumulating evidence implicates a role of NK cells in not only direct killing of tumor cells, but also in cancer immunosurveillance and preventing metastasis to tissues sites. However, at present the distribution, diversity and tissue driven differences in NK cell function are not well characterized which may have an implication on the anti-cancer potential of tissue NK cells. Through collaboration with LiveOnNY our local organ procurement organization, we receive blood, bone marrow (BM), lung, intestines, tonsil and associated lymph nodes (LN) from research consented organ donors. Here we used this unique tissue resource to investigate the distribution, phenotypic, functional and transcriptional diversity of NK cell subsets in human tissues. We found that NK cells are ubiquitously distributed in human tissues comprising up to 40% of the CD45+ CD14/19- cells in blood, BM, spleen and lung, while only a small fraction (up to 2%) in the intestine and the LN. While blood, BM, spleen and lung are dominated by mature NK cells (CD56dim CD16+), majority of the NK cells in intestine and LN are immature (CD56hi CD16-). Age, sex and CMV sero-status do not show any correlation with NK cell distribution or subset frequency in tissues. Notably, NK cell subset distribution seems to drive functional differences between tissue NK cells, with lymphoid site NK cells expressing lower levels of effector molecules granzyme B, TNFα, Prf, Ifnγ and displaying reduced degranulation compared with their counterparts from blood, BM and spleen. For an in-depth analysis of tissue-mediated effects on NK cell subset functionality, we performed whole-transcriptome profiling on immature and mature NK cells isolated from blood, BM, spleen, lung and LN. Our analysis identified several effector molecules and NK cell surface receptors being differentially expressed between immature and mature NK cells. Furthermore, while mature NK cells of blood and tissues have similar transcriptional profiles, the transcriptional profiles of immature blood and tissue NK cells show tissue driven heterogeneity with differential expression of transcription factors, metabolic enzymes and NK cell surface receptors. Interestingly, the transcriptional signature of immature NK cells is reminiscent of the transcriptional signature of tissue resident memory T-cells showing increased expression of CD103, CD49a, CXCR6. We validated the expression of these markers using multiparameter flow cytometry and found that subset of immature NK cells in mucosal sites (lung and intestine) do indeed express markers of tissue residence. Additionally, by applying trajectory projection algorithm on NK cells from tissue sites, we show that resident NK cells comprise a distinct population from immature NK cells. Our study has identified novel, previously unidentified diversity of tissue NK cells. Phenotypic and transcriptional profiling data provide evidence for putative resident NK cells being present in certain tissue sites. Blood NK cells differ from their counterparts in tissues; especially, immature NK cells in tissues may be specifically trained to function in the tissue environment. Finally, due to the uniqueness of phenotypic, functional and transcriptional features of tissue NK cells, they may be more suited to fight cancer in situ in tissues. Citation Format: Pranay Dogra, Takashi Senda, Peter Szabo, Dustin Carpenter, Marta Toth, Puspa Thapa, Mark Snyder, Michelle Miron, Brahma Kumar, Donna L. Farber. Human NK cell distribution memory and residence in tissue sites [abstract]. In: Proceedings of the Fourth CRI-CIMT-EATI-AACR International Cancer Immunotherapy Conference: Translating Science into Survival; Sept 30-Oct 3, 2018; New York, NY. Philadelphia (PA): AACR; Cancer Immunol Res 2019;7(2 Suppl):Abstract nr B153.

1586. Prevalence and Significance of Pre-transplant BK Viremia and Viruria in Deceased and Living Kidney Donors and Kidney Transplant Recipients

BackgroundBK virus (BKV) is a major cause of nephropathy in kidney transplantation. Pre-transplant BKV shedding in the donor or recipient may increase the risk for developing BKV viremia in kidney transplant recipients.MethodsFrom August 2016 to December 2017, we prospectively performed pre-transplant BKV DNA PCR testing on plasma and urine samples from deceased kidney donors procured through Donor Network West, our local organ procurement organization and third largest in the country. We also simultaneously performed pre-transplant BKV DNA PCR testing of plasma and urine from living kidney donors and adult kidney transplant recipients as well as post-transplant surveillance testing of recipients at Stanford University Medical Center.ResultsBKV DNA PCR testing of plasma and urine samples from 212 deceased kidney donors revealed 17 donors that were positive (16 in urine, 1 in plasma; 8.02% BKV DNA detection). Fifty of these specimens went to Stanford kidney transplant recipients, including four donors with BKV viruria (8.00%). During the study period, we obtained complete pre-transplant donor and recipient pairings for 47 deceased and 39 living adult kidney transplant recipients. Of these 86 kidney recipients, none had detectable BKV DNA in pre-transplant donor or recipient plasma specimens, while 10 (four deceased, six living) had BKV DNA detected in the urine. The majority (9/10) were positive in the donor urine, with one positive in the recipient and one in both the recipient and donor. After a minimum follow-up of 5 months, three (30%) had developed BKV viremia, compared with three of the 76 (3.9%, P = 0.009) with negative pre-transplant BKV DNA. The rate of BKV viruria was not significantly different between deceased and living kidney donors (4/47 (8.5%) vs. 6/39 (15.4%), P = 0.32).ConclusionIn one of the largest cohorts in the United States that also includes deceased donor testing, we demonstrate that pre-transplant BKV viruria, particularly of the donor, is associated with development of BKV viremia in kidney transplant recipients. Pre-transplant BKV DNA screening in the urine of kidney donors (deceased and living) may be useful in predicting risk for BKV viremia.Disclosures All authors: No reported disclosures.

Chest computed tomography imaging improves potential lung donor assessment

ObjectiveChest computed tomography (CT) imaging is being increasingly used for potential lung donor assessment. However, the efficacy of CT imaging in this setting remains unknown. We hypothesize that chest CT imaging independently affects the decision-making process in donor lung utilization. MethodsWe conducted a retrospective cohort study of all adult donation after brain death donors managed through our local organ procurement organization from June 2011 to November 2016. An experienced thoracic radiologist independently reviewed donor chest CT and chest x-ray images in a blinded, standardized manner to determine the presence of structural lung disease (eg, emphysema, interstitial lung disease [ILD]) and acute abnormalities (eg, traumatic lung injury [TLI]). Distinct models of lung utilization were fit to groups with initial partial pressure of oxygen (iPaO2) ≤300 mm Hg (suboptimal) and iPaO2 >300 mm Hg (optimal). ResultsThe organ procurement organization managed 753 donors during the study period, with a lung utilization rate ([lung donors/all organ donors] × 100) of 36.5% (275 of 753). Four hundred forty-five (59.1%) donors received chest CT imaging, revealing emphysema (13.7%), ILD (2.5%), and TLI (7.2%). In univariate analysis, findings of TLI (odds ratio [OR], 2.23; 95% confidence interval [CI], 1.08-4.61) were positively associated with lung utilization, whereas findings of emphysema (OR, 0.18; CI, 0.08-0.40) were negatively associated with utilization. In multivariate analysis, CT findings of emphysema (OR, 0.21; CI 0.08-0.54) remained negatively associated with utilization. No potential donors with CT findings of ILD became lung donors. After controlling for chest x-ray findings, chest CT imaging findings of structural lung disease remained negatively associated with utilization (P = .0001). Lung utilization rate in the suboptimal and optimal iPaO2 populations was 35.1% and 41.4%, respectively, and CT findings of emphysema had a significant association with nonutilization in both groups. ConclusionsIn the evaluation of potential lung donors, chest CT imaging findings of structural lung disease, such as emphysema and ILD, have a significant negative association with lung utilization. Our findings suggest that chest CT imaging might be an important adjunct to conventional lung donor assessment criteria.

Is “lung repair centre” a possible answer to organ shortage?—transplantation of left and right lung at two different centres after ex vivo lung perfusion evaluation and repair: case report

Ex vivo lung perfusion (EVLP) has become a reality as a technique to evaluate and recondition lungs from marginal donors. We report the first case on the use of EVLP followed by separate transplantation in two different centres. The local organ procurement organization proposed the lungs of a 53-year-old non-smoker donor who died for cerebral haemorrhage. P/F ratio was 294 after lung recruitment manoeuvres. Oto score was 10. Two centres accepted the grafts for two single transplantations under the condition of EVLP evaluation. After usual retrieval, the bi-pulmonary block was transferred to Centre 1 and EVLP was run as previously described. At the end of the procedure the two lungs were evaluated separately and both judged suitable for transplantation. After cooling and storage on ice, the block was separated on the back table. The left lung was transplanted in a patient with pulmonary fibrosis at Centre 1; surgery was complicated by cardiac arrhythmias that required several defibrillations. The right lung was transferred on ice to Centre 2, 250 km away from Centre 1, and transplanted in a patient with idiopathic pulmonary fibrosis. Thirty months after transplantations Patient 1 and Patient 2 are both alive, in good clinical conditions. This is the first report of the separate use of lungs after EVLP for non-urgent recipients in two different centres. This experience opens the door to a new allocation model with great potentials on organ shortage. Actually, we demonstrated that the perspective of a 'lung repair centre' is feasible and effective.

Lung Focused Resuscitation at a Specialized Donor Care Facility Improves Lung Procurement Rates

Lung procurement for transplantation occurs in approximately 20% of brain dead donors and is a major impediment to wider application of lung transplantation. We investigated the effect of lung protective management at a specialized donor care facility on lung procurement rates from brain dead donors. Our local organ procurement organization instituted a protocol of lung protective management at a freestanding specialized donor care facility in 2008. Brain dead donors from 2001 to 2007 (early period) were compared with those from 2009 to 2016 (current period) for lung procurement rates and other solid-organ procurement rates using a prospectively maintained database. An overall increase occurred in the number of brain dead donors during the study period (early group, 791; late group, 1,333; p < 0.0001). The lung procurement rate (lung donors/all brain dead donors) improved markedly after the introduction of lung protective management (early group, 157 of 791 [19.8%]; current group, 452 of 1,333 [33.9%]; p < 0.0001). The overall organ procurement rate (total number of organs procured/donor) also increased during the study period (early group, 3.5 organs/donor; current group, 3.8 organs/donor; p= 0.006). Lung protective management in brain dead donors at a specialized donor care facility is associated with higher lung utilization rates compared with conventional management. This strategy does not adversely affect the utilization of other organs in a multiorgan donor.

Quality Improvement in Facial Transplantation: Standard Approach for Novel Procedures

With 40 procedures reported to date, facial transplantation (FT) is a viable reconstructive option for patients with severe facial defects.1 A major challenge of FT is developing patient-specific reconstructive strategies, as facial defects can vary widely in potential candidates. This variability and the limited number of procedures performed to date have made the standardization of approaches to FT particularly difficult. The improvement of any process, including FT, relies heavily on standardization if long-term sustainability is to be achieved, and patient safety must remain a top priority in the early stages of surgical innovation. Through teamwork optimization, surgical simulation, methodical use of surgical technology, and the application of efficient perioperative algorithms (Table 1), the senior author (E.D.R) has performed 2 FTs under institutional review board approval. The first was performed in March 2012 and consisted of a total face, double jaw, and tongue transplant in a patient who sustained ballistic midface injury.2 The second was performed in August 2015 and consisted of a total face, eyelids, ears, scalp, and skeletal subunit transplant in a patient who sustained high surface area burns.3 Both distinct facial defects were addressed successfully by FT; surgeries and recovery occurred without incident. The patients present excellent aesthetic, functional, and quality of life outcomes.2,3Table 1.: Standardized Processes in Clinical Facial Transplants Performed by Our Surgical TeamSTANDARD APPROACH TO FACIAL ALLOGRAFT PROCUREMENT, TRANSPLANT, AND SURGICAL TEAM Seventeen mock cadaveric FTs were performed in preparation for both procedures.2,3 Furthermore, 2 research allograft procurements were performed in brain dead donors.2,3 These rehearsals allowed real-time high-fidelity simulation, objective outcomes evaluation, and ensured surgical refinement through repetition. In each simulation, donor and recipient surgical teams work together to reinforce team dynamics and optimize performance before clinical FT. METHODICAL USE OF SURGICAL TECHNOLOGY Computerized surgical planning was incorporated into every simulation opportunity and subsequently integrated into both clinical FTs.2,3 Three-dimensional (3D) models generated from craniofacial computed tomography scans (Fig. 1) are used to identify optimal sites of osteotomy. In addition, personalized cutting guides are designed and 3D-printed for improved intraoperative accuracy.2,3 During surgery, facial allograft perfusion assessment using indocyanine green fluorescent angiography was performed, before transection of allograft source vessels, and upon completion of the procedure to ensure adequate blood flow.2,3Fig. 1.: Methodical use of surgical technology and optimization of team dynamics. A, Computerized surgical planning and design of bone cutting guides for precise guidance of osteotomies. B, Team-based surgical planning and simulation. (Printed with permission from and copyrights retained by Eduardo D. Rodriguez, M.D., D.D.S.).WORKFLOW STANDARDIZATION Standardization of logistical processes that are critical to FT was implemented, including an algorithm for asynchronous face and multiorgan allograft procurement from brain dead donors4 and an algorithm for the safe transfer of multiorgan donors to the FT team’s home institution in collaboration with the local organ procurement organization.4 These algorithms focus on ensuring the integrity of lifesaving solid organ allografts, enhancing surgical team safety, and improving communication between donor and recipient teams. Finally, perioperative nursing workflows have been developed in our most recent series of FT simulations.5 Through constant and objective self-evaluation, we continue to identify opportunities for process improvement. Our experience serves as proof of concept that exhaustive planning, process standardization, and quality improvement are possible for novel surgical procedures with limited worldwide experience.